Progesterone Audit Shilpa Joshi SpR Chemical Pathology Royal Devon and Exeter NHS Foundation Trust

Background It was noticed by the staff in Clinical Chemistry at Royal Devon and Exeter Foundation Trust, that there was increase in serum progesterone requests over the last couple of years Many had either very little or no clinical details provided

At around the same time, The Royal College of Pathologists published in their July 2011 Bulletin: ‘Audit of progesterone requesting in pregnancy of unknown location, June 2009’ carried out at Kingston Hospital NHS Trust

That audit evaluated the nature of requests for progesterone (apart from fertility invsg.) They developed local guidance for requesting progesterone in PUL, wherein progesterone was only needed where serum β-HCG was not declining as expected They developed a software rule to block requests from in- patient admissions/ A&E , which did not have a β-HCG request on the same patients in the past 20 days

A re audit by the same department in February 2011 (published in the same bulletin) showed a remarkable reduction of 93% in serum progesterone tests being analysed They demonstrated an annual cost saving of £830 on progesterone As a result we decided to audit our local progesterone requesting pattern

Local RDE protocol for management of PUL Progesterone (nmol/L) β-HCG (IU/L) <16 >25 Spontaneous resolving pregnancy, check β- HCG in 7 days 16-60 >25 Miscarriage/Ectopic with moderate intervention, β-HCG in 2 days. >60 <1000 Normal intrauterine pregnancy, repeat scan β-HCG >1000 >60 >1000 Ectopic pregnancy with high risk requiring intervention, scan same day

Role of placenta and progesterone in early pregnancy Corpus Luteum (Ovaries) secrete Progesterone maintains foetal viability Foetus + Placenta signal

Aim To examine and compare serum progesterone requests received by the Department of Clinical Chemistry, RDE, in months February and March in the years 2008 and 2011 To be in a position to draft and publish some local guidelines for requesting serum progesterone.

Method Encore data extraction software was used to obtain serum progesterone requests in the months Feb-March in the years 2008 and 2011 Only those progesterones which had an accompanying β-HCG were included in the audit ( serum progesterones requested for investigation/ monitoring of infertility were not included)

Number of progesterones requested in two months in 2008 and 2011

In 2008 68X1=68 13X2=26 2X3= 6 83 women = 100 requests in 2 months In 2011 139X1=139 15X2=30 2X3=6 156 women = 175 requests in 2 months (A progesterone was erroneously added to a male patient’s test profile by the laboratory which was not included in the current audit)

Distribution of progesterone requests in ( 83+156) females according to age groups in Feb-March 2008 &2011 The women ranged from ages 16-46 years in 2008 and 15-44 years in 2011.

Requests in 2008 and 2011 stratified according to departments

A&E requests in 2008 & 2011

Clinical reasons for requesting serum progesterone in 83 women in Feb-March 2008 and 156 women in Feb-Mar 2011   Feb-Mar 2008 (Total=83) Feb-Mar 2011(Total=156) MONITORING TREATMENT IN INFERTILITY 12 5 ? ECTOPIC ? MISCARRIAGE 3 (3.6%) 11 (7%) ?ECTOPIC INCLUDING ABDOMINAL PAIN IN PREGNANCY 36 (43.3%) 45 (28.8%) ECTOPIC 3 ? MISCARRIAGE /PV BLEEDING IN PREGNANCY 15 (18%) 47 (30.1%) MISCARRIAGE 2 THREATENED MISCARRIAGE INCONCLUSIVE SCAN IN PREGNANCY 11 ABDO PAIN OTHERWISE MOLAR PREGNANCY DIAGNOSED 1 PV BLEEDING OTHERWISE RETAINED PRODUCTS 0 (0%) 8 (5%) ?PREGNANT/ PREGNANT 6 NCD 7

Clinical scenarios where the local RDE protocol for management of PUL can be applied 2008 (44) 2011 (67) ? ECTOPIC ? MISCARRIAGE 3 11 ?ECTOPIC INCLUDING ABDOMINAL PAIN IN 36 45 PREGNANCY INCONCLUSIVE SCAN IN PREGNANCY 5

Classification of the above cases according to the local RDE protocol for management of PUL ?Ectopic / PUL in 2008/ 2011 33 cases (2008) + 52 cases (2011) had a single progesterone 11cases (2008) + 15 cases (2011) had more than one progesterone Baseline progesterone + β-HCG Prog. β-HCG Prog. β-HCG <16 >25 Spont. resolving pregnancy, β- HCG in 7 days 16-60 >25 Miscarriage/Ectopic with moderate intervention, β-HCG in 2 days. 6 (2008) + 3 (2011) 4 (2008) + 8 (2011) Prog. β-HCG Prog. β-HCG >60 <1000 Normal intrauterine pregnancy, repeat scan >60 >1000 Ectopic pregnancy with high risk β- HCG >1000 requiring intervention, scan same day 1 (2011) 1 (2008) + 3 (2011)

Progesterone (nmol/L) β-HCG (IU/L) <16 >25 Spontaneous resolving pregnancy, check β- HCG in 7 days 6 cases (2008) of which 4 women miscarried, 2 had decreasing β- HCG with unknown outcomes 3 cases (2011) of which 1 woman was diagnosed with ectopic, 2 had decreasing β-HCG with unknown outcomes

Progesterone (nmol/L) β-HCG (IU/L) 16-60 >25 Miscarriage/Ectopic with moderate intervention, β-HCG in 2 days 4 cases (2008) of which 2 women went to full term, 2 had decreasing β- HCG with unknown outcomes 8 cases (2011) of which 2 women went to full term, 1 had ectopic, 2 miscarried, 3 had decreasing β-HCG with unknown outcomes

Progesterone (nmol/L) β-HCG (IU/L) >60 <1000 Normal intrauterine pregnancy, repeat scan β-HCG >1000 1 case (2011) β-HCG not doubling, Ectopic

Progesterone (nmol/L) β-HCG (IU/L) >60 >1000 Ectopic pregnancy with high risk requiring intervention, scan same day 1 case (2008) which went on to have a full term pregnancy 3 cases (2011) of which 1 had full term pregnancy, whilst the other 2 miscarried,

Clinical reasons (excluding investigation for infertility/ threatened miscarriage) for analysing progesterones, which do not fulfil the local PUL algorithm   Feb-Mar 2008 (Total= 27 ) Feb-Mar 2011(Total= 81) ECTOPIC 3 ? MISCARRIAGE /PV BLEEDING IN PREGNANCY 15 47 MISCARRIAGE 2 ABDO PAIN OTHERWISE MOLAR PREGNANCY DIAGNOSED 1 PV BLEEDING OTHERWISE RETAINED PRODUCTS 8 ?PREGNANT/ PREGNANT 6 NCD 7 12

Conclusions 2008/2011 The audit evaluated a total of 100 serum progesterone tests in Feb-March 2008 and 175 in Feb-March 2011 239 different patients in months of Feb-March 2008 & 2011 had a total of 275 progesterone tests

There was increase in progesterone requests by 75% in 2011 compared to 2008 The major requestor was OBGYN 83/100 (83%) in 2008 and 134/ 175 (76.5%) in 2011 The main reasons for requesting the test was ? Ectopic pregnancy and ? Miscarriage / PV bleeding in pregnancy

Perhaps the algorithm for PUL is being utilised indiscriminately in other clinical scenarios, 32.5% (2008) , 51.9% (2011) In 2008, 10 cases (4 OBGYN+5 GP+1 UNK) had a progesterone requested even though the baseline β-HCG <1. Out these 7 cases were for querying ectopic pregnancy In 2011, 21 cases ( 8GP + 2A&E + 11 OBGYN ) had a serum progesterone even though baseline β-HCG demonstrated that the patients were not pregnant A&E continues to order baseline β-HCG +Progesterone in high proportions

Limitations of the audit It was tricky to evaluate the suitability of the test requests exclusively on the basis of the clinical details available on PTH, which were often insufficient The level of seniority of medical staff requesting progesterones could not be verified , as samples were booked under the consultant leading the team

Request forms from A&E have A&E consultant names printed on the forms, therefore, samples from A&E may have been requested by other departments Also, in cases where progesterone/ β-HCG added at a later time, it was difficult to know the team requesting these tests as samples were booked under A&E Currently there is no clear guidance regarding the clinical conditions meriting a serum progesterone

Recommendations Liaise with OBGYN to encourage use of the PUL algorithm only in those conditions which fit the criteria, and, discourage use in other clinical scenarios Serum progesterone to be not analysed in situations where no clinical/ irrelevant clinical details provided Re audit data probably in a year

References The management of early pregnancy loss (green-top guideline no.25, October 2006): Royal College of Obstetricians and Gynaecologist Audit of progesterone requesting in pregnancy of unknown location, June 2009: The Royal College of Pathologist Bulletin, July 2011, pg 200-203 Expectant management of ectopic pregnancy (revised Feb2010), Guidelines by Child and Women’s Health, Royal Devon and Exeter NHS Trust Donna Day Baird, Clarice R. Weinberg, D. Robert McConnaughey, and Allen J. Wilcox Rescue of the Corpus Luteum in Human Pregnancy Biol Reprod February 2003 68 (2) 448-456

Acknowledgement Dr O’Connor/ Dr Salzmann

Thank you